N-protonation

N Protonation.—Controversy over the site of protonation of amides has been raised anew by Liler. Using u.v. spectroscopy, she has suggested that benzamide is 50 50 O N protonated in 80 % sulphuric acid. However, a considerable weight of evidence has been produced to indicate that protonation or Lewis acid complexation of amides consistently occurs by co-ordination with oxygen. Studies have included the acidity-dependent changes in the tt-tt and n-it u.v. absorption bands of aliphatic amides kinetic evidence based on rate data for acid-catalysed amide hydrolysis in both dilute and concentrated acid an n.m.r. study of proton exchange rates, where for A -methylacetamide the molar ratio of 0 N protonated species exceeds 10 a n.m.r. study of adducts of boron trifluoride and antimony pentachloride with N-labelled ureas, where the hybridization-dependent —H coupling constants were inconsistent with N-co-ordination  

An alternative preparation of amide acetals is based on the reaction of secondary amines with dialkoxymethylammonium salts when secondary 

Secondary amides are oxidized, as their iV-trimethylsilyl derivatives, to the corresponding hydroxamic acids by a molybdenum oxide-HMPA complex. NN-disubstituted thiocarbamoyl chlorides or bromides are easily prepared by direct reaction of the corresponding thioformamides with elemental halogen. 

Several AT-t-butoxyamido radicals and amido free radicals themselves - have been generated, and observed by e.s.r. spectroscopy a it ground-state 

A combination of Fourier transform and partially relaxed Fourier transform spectroscopy has been used to determine steric compression shifts in aliphatic amides and oximes, allowing, inter alia, a sensitive study of internal rotation. 

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Various other heteroatom-substituted earbocations were also found to be activated by superacids. a-Nitro and a-cyanocarbenium ions, R2C N02 or R2C CN, for example, undergo O- or N-protonation, respectively, to dicationic species, decreasing neighboring nitrogen participation, which greatly enhances the electrophilicity of their carbo-... 

The + 1 rule should be amended to read When a proton H is coupled to Hj etc and Jac Jad the original signal for H is split into n + peaks by n protons each of these lines is further split into n + peaks by n pro tons and each of these into n + lines by n Hj protons and so on Bear in mind that because of overlapping peaks the number of lines actually observed can be less than that expected on the basis of the splitting rule... 

Step 5 Dissociation of the N protonated form of the tetrahedral intermediate to give ammonia and the protonated form of the carboxylic acid... 

Step 4 Dissociation of N protonated form of tetrahedral intermediate... 

Equivalent Weights Acid-base titrations can be used to characterize the chemical and physical properties of matter. One simple example is the determination of the equivalent weighf of acids and bases. In this method, an accurately weighed sample of a pure acid or base is titrated to a well-defined equivalence point using a mono-protic strong acid or strong base. If we assume that the titration involves the transfer of n protons, then the moles of titrant needed to reach the equivalence point is given as... 

The ions so produced are separated by their mass-to-charge (m/z) ratios. For peptides and proteins, the intact molecules become protonated with a number (n) of protons (H+). Thus, instead of the true molecular mass (M), molecular ions have a mass of [M + uH]. More importantly, the ion has n positive charges resulting from addition of the n protons [M + uH]". Since the mass spectrometer does not measure mass directly but, rather, mass-to-charge (m/z) ratio, the measured m/z value is [M + uH]/u. This last value is less than the true molecular mass, depending on the value of n. If the ion of true mass 20,000 Da carries 10 protons, for example, then the m/z value measured would be (20,000 + 10)/10 = 2001. 

N-protonation the absolute magnitude of the Ad values is larger than for Af-methylation <770MR(9)53>. Nuclear relaxation rates of and have been measured as a function of temperature for neat liquid pyridazine, and nuclear Overhauser enhancement has been used to separate the dipolar and spin rotational contributions to relaxation. Dipolar relaxation rates have been combined with quadrupole relaxation rates to determine rotational correlation times for motion about each principal molecular axis (78MI21200). NMR analysis has been used to determine the structure of phenyllithium-pyridazine adducts and of the corresponding dihydropyridazines obtained by hydrolysis of the adducts <78RTC116>. 

Thiochrome (2,7-dimethyl-5//-thiachromine-8-ethanol 3,8-dimethyl-2-hydroxyethyl-5//-thiazolo[2,3 l, 2 ]pyrimido[4, 5 -d]pyrimidine [92-35-3] M 262.3, m 227-228 , pK st 5.8 (thiazol-N protonation). Crystd from chloroform. 

The mechanism for acid-catalyzed hydrolysis of amides involves attack by water on the protonated amide. An inqjortant feature of the chemistry of amides is that the most basic site in an amide is the carbonyl oxygen. Very little of the N-protonated form is present. The major factor that contributes to the stability of the O-protonated form is the... 

TT-electron delocalization over the O—C—N system. No such delocalization is possible in the N-protonated form. 

Amides are weak bases with pA values in the range of 0 to —2. When amide resonance is prevented, as in l-azabicyclo[2.2.2]octanone, N-protonation is preferred. ... 

It is interesting to note that the hydrolysis of certain Schiff bases in weakly acidic solutions shows a similar mechanism (22). N-protonated substituted benzylidene-t-butylamines react with hydroxide ions to amino alcohols in the rate-determining step, and at lower pH the rate is almost entirely determined by attack of water on the protonated Schiff bases as a consequence of the rapidly decreasing concentration of hydroxide ions. 

The above assumes that C protonation is not excluded for steric reasons. Thus N protonation takes place with derivatives of dehydroquinuclidine and the alkaloids neostrychnine and trimethylconkurchine (( ). N protonation was also believed to occur in the case of 2-N-hexamethyleneimino-bicyclo[l,2,2]-2-heptene, which was believed to give the nortricyclene derivative (6) on protonation with perchloric acid. Later work, however, showed the salt to be the results of C protonation (15) and to have structure 7. 

Electrostatic potential map for N protonated imidazole shows most positively-charged regions (in blue) and less positively-charged regions (in red). 

Compare energies for the two alternative conjugate acids of methyl acetate (protonated methyl acetate and methoxy protonated methyl acetate) and dimethylacetamide (N-protonated dimethylacetamide and 0-protonated dimethylacetamide). Which acid in each pair is more stable Draw resonance contributors for the more stable conjugate acid for each system. 

Which nitrogen in each molecule is more basic Compare energies of the alternative conjugate acids (Nprotonated imidazole, NH protonated imidazole, N protonated pyrazole and NH protonated pyrazole). Which compound, imidazole or pyrazole, is more basic Compare the energies of protonation (leading to the favored conjugate acid in each case). Rationalize your result. 

Examine pyrrole s highest-occupied molecular orbital (HOMO) to see if your can predict the most favorable protonation site. Which of the pyrrole s conjugate acids (N protonated, C2 proto noted, C3 proto noted pyrrole) is lowest in energy Examine electrostatic potential maps to see if the lowest-energy form is also that in which the positive charged is best delocalized. Rationalize your result using resonance arguments. What should be the favored substitution product ... 

The structures of pyrrolo[l,2-c]pyrimidine 139 and its N-protonated form 140 were obtained from MP2/6-31G calculations (Scheme 92) [99JOC7788]. Proton affinities computed at the same level reveal that N-protonation is slightly preferred over protonation at the C7 position. The most stable tautomers of 2-substituted 5-methyl-7-hydroxy-l,2,4-tiiazolo[l,5-a]pyrimidine 141 were... 

ProtokoU, n. minutes, record protocol. Protonen-bescbleunigung, /. acceleration of protons, -geseboss, n. proton projectile, -wandening, /. traveling of protons. Protoplasma-bewegung, /. protoplasmic motion. -kSrper, m. protoplasmic body, -strahl, m. protoplasmic ray. 

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